An updated classification of thrombotic microangiopathies and treatment of complement gene variant-mediated thrombotic microangiopathy

Abstract

Conditions presenting with signs of thrombotic microangiopathies (TMAs) comprise a wide spectrum of different diseases. While pathological hallmarks are thrombosis of arterioles and capillaries, clinical signs are mechanical haemolysis, thrombocytopenia and acute renal injury or neurological manifestations. The current classification of various syndromes of TMA is heterogeneous and often does not take the underlying pathophysiology into consideration. Therefore we propose a simplified classification based on the aetiology of different syndromes leading to TMA. We propose to categorize different TMA syndromes in hereditary and acquired forms and classify them based on the genetic background or underlying conditions. Of course, this classification is not always distinctly applicable in each case and from time to time reassessment of the established diagnosis is strongly recommended. The recommended treatment of TMA in the past was plasma exchange (PE). However, recently, the terminal complement inhibitor eculizumab became commercially available and has shown promising results in different open-label studies and case series. In our centre, first-line therapy is PE; however, patients are instantly switched to complement inhibitory therapy in case of treatment failure or intolerance.

Sex Differences in Clinical Presentation and Outcomes among Patients with Complement-Gene-Variant-Mediated Thrombotic Microangiopathy

“…Plasma exchange has been used as a first line of therapy since it became available as a routine therapy in the mid-1980s. Since 2012, eculizumab has been available, and it is used in cases of failure or intolerance of PE for all patients with suspected or proven cTMA; a detailed description of the treatment approach can be found in Aigner et al [1].…”

“…Complement-gene-variant-mediated thrombotic microangiopathy (cTMA or atypical hemolytic uremic syndrome, aHUS) is a rare hereditary and devastating disease, resulting in kidney failure and premature death [1][2][3]. It is characterized by microangiopathic hemolytic anemia, thrombocytopenia, and organ damage due to an alternative complement pathway overactivation within the vascular CFH-H8 was diagnosed.…”

Two cases of carfilzomib‐induced thrombotic microangiopathy successfully treated with Eculizumab in multiple myeloma

“…When anemia is accompanied with thrombocytopenia, acute kidney injury, high blood pressure, neurological or unexplained extrarenal symptoms TMA should be considered. TMA includes a group of etiologically diverse diseases: Primary TMA, which include atypical HUS (aHUS) or thrombotic thrombocytopenic purpura (TTP) and secondary TMA and infection-associated TMA, involving Shiga-toxin-producing Escherichia coli-associated hemolytic uremic syndrome (STEC-HUS) [ 6 , 13 , 14 ]. TTP, in contrast to other TMA forms, is defined by decreased activity of the vWF-cleaving enzyme ADAMTS13 [ 6 ].…”

Atypical Hemolytic Uremic Syndrome in the Setting of Acute Clostridium difficile Colitis

“…It was formerly classified into typical HUS, which is caused by Shiga toxin-producing E. coli and considered the most common type in children, and atypical HUS, or non-Shiga toxin HUS, which accounts for most of the adult cases [ 7 ]. The new classification was developed based on the pathophysiology and precipitating factors [ 8 ]; hereditary causes include complement gene mutations and cobalamin C deficiency. Acquired causes involve autoantibodies to complement factors, drug-induced, and infection.…”